1. Field of the Invention:
This invention relates to and has among its objects a novel immune globulin and novel methods for its production. Particularly, the invention is concerned with an intravenously injectable immune globulin having a high titer of naturally occurring antibody to varicella-zoster virus (VZV). Further objects of the invention will be evident from the following description wherein parts and percentages are by weight unless otherwise specified.
2. Description of the Prior Art:
Hyperimmune serum globulins, i.e., immune serum globulins having high titers of a particular antibody, are therapeutically useful in treating patients deficient or in need of that particular antibody. For example, tetanus hyperimmune globulin is useful in treating tetanus, and rabies hyperimmune globulin, rabies. It is well known that hyperimmune globulins can be produced from plasma or serum obtained from selected donors who have significantly higher titers for a specific antibody than is normally found in the average population. These donors have either been recently immunized with a particular vaccine (U.S. Pat. No. 4,174,388) or else they have recently recovered from an infection or disease [Stiehm, Pediatrics, Vol. 63, No. 1, 301-319 (1979)].
Although clinical disease from VZV is not common among the general population, it is encountered very frequently in certain susceptible groups of patients. Immunosuppressed organ transplant and cancer patients have been identified as having an unusually high risk of acquiring severe, and frequently fatal, VZV infection. Zaia et al in The Journal of Infectious Diseases, Vol. 137, No. 5, 601-604 (1978) disclosed a practical method for preparation of VZV immune globulin for intramuscular administration. Outdated blood was screened for complement-fixing antibody to VZV. About 15% of the plasma units had a complement-fixation titer equal to or greater than 1:16, with about 7.5% greater than or equal to 1:32.
A report published in Morbidity and Mortality Weekly Report, Vol. 33 (No. 7), 84-100 (Feb. 24, 1984) [see also, J. Amer. Med. Assn., 251 (11), 1401 (1984)] discloses a statement by the Immunization Practices Advisory Committee on the use of a varicella-zoster immune globulin (VZIG) product. This commercially available VZIG product is intended to be administered intramuscularly and should never by administered intravenously. See Morbidity and Mortality Weekly Report, 33 (7), 84-100 at page 96 (1984). See also J. Amer. Med. Assn., 251 (11), 1401 at page 1413 (1984).
S. G. Paryani et al, J. Pediatrics, 105 (2), 200-205 (1984) and Amer. J. Med., 124-127 (Mar. 30, 1984) disclose the results of a study which showed that administration of a modified immune serum globulin product that can be given intravenously (Gamimune.RTM., Cutter Biological - Miles Laboratories, Inc., Berkeley, Calif.) to patients brought about a titer of antibody to VZV comparable to that brought about by intramuscular administration of VZIG. Table I in J. Pediatrics, 105 (2), 200 at 201 (1984) illustrates the comparison of VZV antibody titers of VZIG and IGIV lots used in the study wherein the titers were determined by three methods, namely, radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA) and indirect fluorescent antibody assay (IFA). This table shows that the ELISA VZV antibody titer of VZIG (1:1.7.times.10.sup.6) is about 18-fold that of IGIV (1:97,000). Still, however, there is a need for a VZV immune globulin product having a higher than normal titer of antibody to VZV that may be administered intravenously.